Showing papers by "Eva S. Schernhammer published in 2005"

Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer

Abstract: cer were 1.10 (95% CI, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.620.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49-0.95) for more than 14 aspirin per week (P.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31-0.71).Asimilardose-responserelationshipwasfoundfornonaspirinNSAIDs(P=.007 fortrend).Theincidenceofreportedmajorgastrointestinalbleedingeventsper1000personyears also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week.

Taking their own lives -- the high rate of physician suicide.

Abstract: It has been known for some time that suicide rates among doctors are higher than those in the general population, writes Dr. Eva Schernhammer. The gap in suicide rates evidently begins as early as medical school, where overall suicide rates are higher than in the age-matched population.

Epidemiology of Urinary Melatonin in Women and Its Relation to Other Hormones and Night Work

Abstract: Objective: Light exposure during night work suppresses melatonin production, and night work has been associated with an increased cancer risk. There is little information, however, about the interrelationships of night work, urinary melatonin levels, and levels of plasma steroid hormones in women. Method: We examined the reproducibility of morning urinary measurements of 6-sulfatoxymelatonin over a 3-year period in 80 premenopausal women. We assessed correlations between average urinary melatonin and plasma steroid hormone levels and evaluated potential associations between night work and hormone levels, using current and long-term shift work information from two large, prospective cohorts, the Nurses' Health Study cohorts. Results: The intraclass correlation for creatinine-adjusted 6-sulfatoxymelatonin was 0.72 (95% confidence interval, 0.65, 0.82). We found significantly increased levels of estradiol after longer durations of night work (geometric mean levels of estradiol, 8.8 pg/mL for women who never worked night shifts versus 10.1 pg/mL for women who worked 15 or more years of night shifts; P for trend = 0.03). We observed a significant inverse association between increasing number of nights worked within the 2 weeks preceding urine collection and urinary melatonin levels ( r = −0.30, P = 0.008), but no association of recent night work with estradiol ( r = 0.10, P = 0.41). Conclusion: A single morning urinary melatonin measurement is a reasonable marker for long-term melatonin levels among premenopausal women. Women who work on rotating night shifts seem to experience changes in hormone levels that may be associated with the increased cancer risk observed among night-shift workers.

Urinary melatonin levels and breast cancer risk

Abstract: Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. In logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.

Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk

Abstract: Background: Earlier data support the hypothesis that the relation between circulating insulin-like growth factor-I (IGF-I) levels and breast cancer risk differs by menopausal status. The strong association of IGF-I with height in childhood and weak or no association between adult levels and adult height also suggest that IGF levels in young women may better reflect an exposure time period of importance to breast cancer. Few studies have assessed IGF binding protein-1 (IGFBP-1) or free IGF and breast cancer risk. Materials and Methods: We conducted a large case-control study nested within the prospective Nurses' Health Study. Plasma concentrations of IGF-I, free IGF, IGFBP-3, and IGFBP-1 were measured in blood samples collected in 1989 to 1990. Eight hundred women were identified who had a diagnosis of invasive or in situ breast cancer after blood collection, up to 1998, 27% of whom were premenopausal at blood collection. To those 800 women, one to two controls were age-matched for a total of 1,129 controls. We used logistic regression models to estimate the relative risk (RR) of breast cancer associated with IGF levels. Findings: Among postmenopausal women, neither IGF-I, IGFBP-3, IGFBP-1, nor free IGF was associated with breast cancer risk [RRs, top versus bottom quintile: IGF-I, 1.0; 95% confidence interval (95% CI), 0.7-1.4; IGFBP-3, 0.8; 95% CI, 0.6-1.1; IGFBP-1, 0.9; 95% CI, 0.6-1.5; and free IGF, 1.0; 95% CI, 0.6-1.4]. Among premenopausal women, IGFBP-3, IGFBP-1, and free IGF similarly were not associated with breast cancer risk (RRs, top versus bottom quintile: IGFBP-3, 1.2; 95% CI, 0.8-2.3; IGFBP-1, 1.5; 95% CI, 0.8-3.0; and free IGF, 1.1; 95% CI, 0.7-2.1). Higher IGF-I plasma levels, however, were associated with a modestly elevated breast cancer risk (RR, 1.6; 95% CI, 1.0-2.6) among the premenopausal women, with a stronger association among premenopausal women ages ≤50 (RR, 2.5; 95% CI, 1.4-4.3); further adjustment for IGFBP-3 did not greatly change these estimates. Interpretation: Circulating IGF-I levels seem to be modestly associated with breast cancer risk among premenopausal women, but not among postmenopausal women. IGFBP-3, IGFBP-1, and free IGF are not associated with breast cancer risk in either premenopausal or postmenopausal women in this cohort.

Sugar-Sweetened Soft Drink Consumption and Risk of Pancreatic Cancer in Two Prospective Cohorts

Abstract: Background: A history of diabetes mellitus and a diet high in glycemic load are both potential risk factors for pancreatic cancer. Sugar-sweetened soft drinks are a prevalent source of readily absorbable sugars and have been associated with an increased risk of obesity and diabetes. We investigated whether higher consumption of sugar-sweetened soft drinks increases the risk of pancreatic cancer. Methods: We examined the relation between consumption of sugar-sweetened soft drinks and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 88,794 women and 49,364 men without cancer at baseline, we documented 379 cases of pancreatic cancer during up to 20 years of follow-up. Soft drink consumption was first assessed at baseline (1980 for the women, 1986 for the men) and updated periodically thereafter. Results: Compared with participants who largely abstained from sugar-sweetened soft drinks, those who consumed more than three sugar-sweetened soft drinks weekly experienced overall a multivariate relative risk (RR) of pancreatic cancer of 1.13 [95% confidence interval (95% CI), 0.81-1.58; P for trend = 0.47]. Women in the highest category of sugar-sweetened soft drink intake did experience a significant increase in risk (RR, 1.57; 95% CI, 1.02-2.41; P for trend = 0.05), whereas there was no association between sweetened soft drink intake and pancreatic cancer among men. Among women, the risk associated with higher sugar-sweetened soft drink was limited to those with elevated body mass index (>25 kg/m2; RR, 1.89; 95% CI, 0.96-3.72) or with low physical activity (RR, 2.02; 95% CI, 1.06-3.85). In contrast, consumption of diet soft drinks was not associated with an elevated pancreatic cancer risk in either cohort. Conclusion: Although soft drink consumption did not influence pancreatic cancer risk among men, consumption of sugar-sweetened soft drinks may be associated with a modest but significant increase in risk among women who have an underlying degree of insulin resistance.

Depressive Symptoms and Prospective Incidence of Colorectal Cancer in Women

Abstract: The authors examined depressive symptoms and prospective incidence of colorectal cancer and distal colorectal adenomas in 81,612 women without prior cancer from the Nurses' Health Study; 400 cases of colorectal cancer and 680 distal colorectal adenomas accrued between 1992 and the year 2000. Depressive symptoms were assessed in 1992 and 1996 with the five-question Mental Health Index (MHI-5), a subscale of the Short-Form 36 health status survey. Scores ranged from 0 to 100, and women with scores between 0 and 52 were defined as having significant depressive symptomatology. The authors also created four categories across the range of Mental Health Index scores: 0-52, 53-75, 76-85, and 86-100 (referent). Cox proportional hazards models were used to analyze the extent of depressive symptoms and colorectal events. Analyses were stratified by body mass index. In multivariate analyses with updated exposure, women with the highest levels of depressive symptoms had an elevated risk of incident colorectal cancer (hazard ratio = 1.43, 95% confidence interval: 0.97, 2.11) compared with women with the lowest levels of symptoms (p(trend) = 0.04). Associations appeared stronger in overweight women. However, depressive symptoms were unrelated to risk of colorectal adenomas. Associations are consistent with a possible role in late promotion of the disease.

Prostate cancer and prostate-specific antigen (PSA) screening in Austria.

Abstract: The possible effect of prostate-specific antigen (PSA) testing on prostate cancer mortality has remained controversial, despite the test’s widespread application. We examined age-specific mortality trends for prostate cancer in Austria before and after the introduction of (opportunistic) PSA testing, to ask whether PSA screening reduces prostate cancer mortality in a uniform cohort of men with equal access to health care. Prostate cancer mortality data covering all 9 federal states of Austria were analysed from 1970 to 2002. PSA testing became widely available in Austria not before 1989. Tyrol, one of the nine federal states of Austria, independently launched a mass prostate cancer prevention project in 1993. We applied join-point regression models to identify changes in the slope of age-specific mortality trends in selected age groups (50–59, 60–69, 70–79, and 80–89 years) and calculated the annual percent change (APC) in mortality between 1970 and 2002 for Tyrol and the rest of Austria separately. After 12 years of follow-up, we were not able to observe a significant reduction in prostate cancer mortality since the introduction of the PSA test in the age groups of 50–59, 60–69, and 80–89 years. A significant decrease was found in the age group of 70–79 (Austria without Tyrol 1989 through 2002: APC, –2.36; 95% CI, –3.38 to –1.34; Tyrol 1991 through 2002: APC, –6.42; 95% CI, –8.92 to –3.86). In this age group the join points 1989 and 1991 cannot be related to PSA testing. PSA screening does not appear to reduce prostate cancer mortality in a uniform cohort of men with equal access to health care. However, given the long lead-time for prostate cancer, even longer follow-up may still be needed to detect any important trends.

Phase I/II study of oral etoposide plus GM-CSF as second-line chemotherapy in platinum-pretreated patients with advanced ovarian cancer

Abstract: The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities of chronic oral etoposide given on days 1–10 followed by rescue with subcutaneous (s.c.) granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 12–19 as second-line chemotherapy in platinum-pretreated patients (pts) with advanced ovarian carcinoma. Cohorts of three to six pts were treated with doses of oral etoposide from 750 mg m−2 cycle−1 escalated to 1250 mg m−2 cycle−1 over 10 days, every 3 weeks. Subcutanous GM-CSF, 400 μg once daily, days 12–19, was added if dose-limiting granulocytopenia was encountered. In total, 18 pts with a median Karnofsky index of 80% (range, 70–100%) and a median time elapsed since the last platinum dose of 10 months (range, 1–24 months), 30% of whom showed visceral metastases, were treated at four dose levels (DLs) of oral etoposide on days 1–10 of each cycle as follows: DL 1, 750 mg m−2 cycle−1, without GM-CSF, three pts; DL 2, 1000 mg m−2 cycle−1, without GM-CSF, three pts; DL 3, 1000 mg m−2 cycle−1, with GM-CSF, six pts; and DL 4, 1250 mg m−2 cycle−1, with GM-CSF, six pts. All pts were assessable for toxicity and 16 pts for response. Dose-limiting toxicity (DLT) was reached at DL 4 by three of six pts, showing World Health Organization (WHO) toxicity grade 4. One patient died from gram-negative sepsis associated with granulocytopenia grade 4. Two more pts developed uncomplicated granulocytopenia grade 4. Thus, we recommend that DL 3 can be used for further phase II evaluation (i.e. oral etoposide 1000 mg m−2 cycle−1, days 1–10, followed by s.c. GM-CSF 400 μg, days 12–19). The clinical complete or partial responses in each patient cohort were: DL 1, one of three pts; DL 2, one of three pts; DL 3, three of five pts; and DL 4, two of five pts. In conclusion, in this phase I/II study, we defined the MTD and the dose recommended for the therapy with oral etoposide given over 10 days followed by s.c. GM-CSF in platinum-pretreated patients with advanced ovarian cancer. Our data demonstrate encouraging activity of this regimen and strongly support its further investigation in a phase II study.

Dr. Schernhammer Replies

Abstract: TO THE EDITOR: Physician suicide rates and suggestions for future studies were nicely reviewed by Eva S. Schernhammer, M.D., Dr.P.H., and Graham A. Colditz, M.D., D.P.H. (1). However, they might consider further evaluation of the “risk factors relating to the working environment” (p. 2300). We have reported on outcomes of impaired physicians for nearly 25 years and have followed all impaired Florida physicians since 1995 (2, 3). Physician drug abuse has been linked to suicide (4, 5). We suggested that not all physician specialties are equally affected by drug abuse and dependence. Similarly, suicide may affect one medical specialty more than another. We have suggested workplace evaluations, starting with a history of drug exposure in the operating and emergency rooms and intensive care units. Anesthesiologists are significantly overrepresented among Florida physicians with substance use disorders. They represent only 5.6% of the total licensed physicians but almost 25% of the physicians with substance use disorders. Access to drugs of abuse has been the major theory advanced to explain this. However, we have proposed that unintended second-hand environmental exposure puts anesthesiologists at increased risk (6). We also recently demonstrated the presence of propofol and fentanyl in operating room air after intravenous administration (7). Secondhand exposure is a fact in some medical workplaces. It was not surprising that anesthesiologists and other physicians exposed to fentanyl in the workplace represented 90% of the fentanyl abusers in Florida. Studies in progress include sampling anesthesiologists’ blood during work in cardiovascular surgery, an environment where high doses of fentanyl are routinely used. Environmental exposure may explain the high rates of addiction among anesthesiologists and why recovery for anesthesiologists often necessitates giving up their work in operating rooms and even changing medical specialties. Prevention of physician opioid abuse and dependence appears to be linked to identifying sources of secondhand exposure and preventing exposure from occurring or by minimizing exposure, as was done with nitrous oxide. Environmental exposure may also prove to be an important factor in suicide attempts, relapses, and prevention. We would strongly suggest that new and important data from the analysis of Drs. Schernhammer and Colditz be expanded to include medical subspecialty and secondhand exposure.